We have previously shown that complement fragment C3b interacts with IgG to form a stable covalent complex. We have demonstrated that formation of these complexes can proceed under plasma conditions and occurs on serum-treated soluble and particulate immune complexes, including bacterial pathogens. C3b residues in such complexes are protected from usual control mechanisms, support exaggerated alternative pathway activity, and are capable of high affinity interactions with human phagocytes which elicit internalization responses. C3b-IgG complexes display unique opsonic activity not reproduced by C3b and IgG randomly located on the surface of target particles. During the last year, we have characterized the behavior the C3b receptor of polymorphonuclear leukocytes in states known to cause internalization. We have shown that this receptor recycles through a pre-lysosomal compartment unless multi-valently ligated. In an attempt to dissect the unique opsonic effects of C3b-IgG complexes, and C3b in general, we have shown that multi-valent preligation of CR1 in human macrophages significantly upregulates subsequent IgGmediated phagocytosis of particles not bearing C3b. The role of specific IgG in "focusing" and amplifying complement fragment deposition, with resultant enhanced opsonization, phagocytosis, and killing of a human pathogen has been examined with Cryptococcus neoformans. Here, the presence of a small number of IgG residues on the cryptococcal capsule elicits a marked increase in phagocytosis and killing, but only if present at the moment of complement activation. In an effort to probe the influence of non-immune ambient IgG on complement-mediated opsonization, we have also studied the observed complement opsonization defects in multiple myeloma sera and in impact of exogenous supraphysiologic IgG infusions on complement- dependent blood stream clearance in an in-vivo model.